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Asymmetric Epoxidation of Allylic Alcohols Catalyzed by Vanadium–Binaphthylbishydroxamic Acid Complex Masahiro Noji, Toshihiro Kobayashi, Yuria Uechi, Asami Kikuchi, Hisako Kondo, Shigeo Sugiyama, and Keitaro Ishii J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00185 • Publication Date (Web): 25 Feb 2015 Downloaded from http://pubs.acs.org on March 2, 2015

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The Journal of Organic Chemistry

Asymmetric Epoxidation of Allylic Alcohols Catalyzed by Vanadium–Binaphthylbishydroxamic Acid Complex Masahiro Noji,* Toshihiro Kobayashi, Yuria Uechi, Asami Kikuchi, Hisako Kondo, Shigeo Sugiyama, and Keitaro

Ishii

Department of Life and Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo

204-8588, Japan

[email protected] GRAPHICAL ABSTRACT

ABSTRACT: A vanadium–binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of

allylic alcohols is described. The optically active binaphthyl-based ligands BBHA 2a and 2b were synthesized from (S)-1,1′-binaphthyl-2,2′-dicarboxylic acid and N-substituted-O-trimethylsilyl (TMS)-protected hydroxylamines via a

one-pot, three-step procedure.

The epoxidations of 2,3,3-trisubstituted allylic alcohols using the vanadium complex

of 2a were easily performed in toluene with a TBHP water solution to afford (2R)-epoxy alcohols in good to excellent enantioselectivities. INTRODUCTION 1 ACS Paragon Plus Environment

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The asymmetric epoxidation of allylic alcohols is an attractive method for the synthesis of chiral epoxy alcohols, which are useful chiral building blocks for the production of pharmaceuticals and agrochemicals.1

The

Katsuki–Sharpless asymmetric epoxidation of allylic alcohols is reliable method of obtaining synthetically useful chiral epoxy alcohols.2

The epoxidation gives very high asymmetric induction for various types of allylic alcohols.

The enantioselectivity depends only on the chirality of L-(+)-, or

structure of the allylic alcohols.

the

epoxidation

is

conducted

D-(−)-tartrates

as ligands, independent of the

Therefore, the absolute configuration of the products can be predicted. Although

using

commercially

available

titanium

tetraisopropoxide,

tartrate,

and

tert-butylhydroperoxide (TBHP) as an oxidizing agent, it requires strict anhydrous conditions.

Recently, the vanadium–chiral hydroxamic acid (V–HA) complex-catalyzed asymmetric epoxidation of allylic

alcohols with TBHP has also become a highly potent approach to obtaining chiral epoxy alcohols.

The advantage of

the V–HA complex-catalyzed method is its simple reaction procedure, which can be conducted in aqueous TBHP solution, rather than under anhydrous conditions. Since the first report by Sharpless,3 the V–HA complex-catalyzed system has been extensively studied for the last decade.4–7

Yamamoto has reported C2-symmetric cyclohexane

diamine-based chiral bishydroxamic acid (BHA) ligands.8

The vanadium–BHA system exhibited excellent

enantioselectivities for a wide range of substituted allylic alcohols. The recent application of BHA ligands for Mo-,

Zr-, Hf-, and W-catalyzed systems demonstrated that the C2-symmetric chiral BHA ligand was very useful for asymmetric oxidations of sulfides, simple alkenes, homoallylic alcohols, and allylic amine derivatives.9

Axially chiral C2-symmetric binaphthyl derivatives have been recognized as a privileged chiral ligand for many

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enantioselective reactions.10

The C2-symmetric chiral auxiliaries minimize the possibility of diastereomeric

interactions at the transition state and are therefore useful for obtaining high enantiomeric excesses and for elucidating the mechanism of asymmetric induction. 11 The steric bulkiness and structural rigidity of naphthalene rings would be

effective for the production of large asymmetric space.

to adapt a wide range of substrates.

The flexibility of the binaphthyl axis enable the chiral ligand

This induced-fit property12 would also be a great advantage for the asymmetric

reaction. Herein, we report the vanadium–binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric

epoxidation of allylic alcohols. RESULTS AND DISCUSSION

The BBHA ligands were synthesized via a one-pot, three-step procedure. The method involved (i) the preparation of the acid chloride of (S)-1,1′-binaphthyl-2,2′-dicarboxylic acid13 (1) followed by (ii) the reaction of the N-substituted-O-TMS protected hydroxylamines and then (iii) the removal of the TMS groups from the amide.

Chromatographic purification and recrystallization gave pure BBHA ligands 2a and 2b in 65% and 54% chemical

yields from (S)-1 (Scheme 1).

Scheme 1. Synthesis of binaphthylbishydroxamic acid (BBHA)

1

H NMR spectra of 2a and 2b in CDCl3 at room temperature showed broad signals, probably because of the 3 ACS Paragon Plus Environment

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structural rigidity of the amide linkage and hydrogen bonding. Therefore, most of the 13C NMR signals of 2a and 2b were not observed. NMR measurements at 80 °C improved the situation with regard to the broad signals in the 1H

and

13

C spectra of 2a and 2b. However, the structure assignments on the basis of the aromatic NMR signals

remained difficult.

Consequently, single-crystal X-ray diffraction analysis was used to ascertain the structure and

conformation of BBHA ligands 2a and 2b.

A single crystal of 2a was obtained by slow evaporation from toluene solution at room temperature.

Similarly, a

single crystal of 2b was prepared from EtOH–THF solution. The molecular structures of 2a and 2b were determined by single-crystal X-ray diffraction analysis.14

The crystal prepared from 2a contained one toluene molecule per 2a.

The dihedral angle of the binaphthyl axis, C2-C1-C1′-C2′, of 2a and 2b was 85° and 70°, respectively. Intramolecular hydrogen bonds between the carbonyl oxygen and hydroxyl group were observed in both structures,

and the oxygen–oxygen distances were 2.6–2.7 Å.

In the crystal of 2a with toluene, the hydroxamic acid moieties

were transoid structures and the torsional angles of HO–N–C=O were 170° and 175°.

In contrast, cisoid and transoid

structures were observed in the crystal structure of 2b and the torsional angles were 14° and 167°, respectively.

The

cisoid hydroxamic groups formed intramolecular stacking structures between the naphthalene and benzene rings.15

BBHA 2a appears to have a larger asymmetric space than 2b, and we employed 2a for initial examination of the asymmetric epoxidation.

To optimize the epoxidation conditions using BBHA 2a, allylic alcohol 3a was used as a model substrate.

The

vanadium/ligand ratio, solvent, and vanadium compounds were investigated using 5 mol% of vanadium compound;

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the results are reported in Table 1.

A typical reaction procedure was as follows: BBHA 2a and 5 mol% of vanadium

compound were stirred in the solvent at 20 °C for 24 h, whereupon 1.5 equiv of TBHP water solution and then allylic

alcohol 3a were added. The mixture was stirred at 20 °C until the complete consumption of allylic alcohol 3a or 24 The reaction was then quenched by adding saturated aqueous Na2SO3 solution; subsequent

h of reaction time.

extraction and chromatographic purification gave epoxy alcohols 4a and recovered 3a.

was determined by chiral-stationary-phase HPLC analysis.

The enantiomeric excess (ee)

The absolute stereochemistry of (2R,3R)-4a was

determined by comparison of the chiroptical property with the literature data.16

Table 1. Optimization of Vanadium/Ligand Ratio, Solvent, and Vanadium Compounds

Ph

OH

Bn N OH

5 mol% V compound (S)-BBHA 2a 1.5 equiv TBHP (in water)

O O Ph

solvent (0.1 mol/L) 20 oC, time

3a

O

OH

N OH Bn

(2R,3R)-4a

(S)-BBHA 2a

a

entrya

vanadium (5 mol%)

BBHA 2a (mol%)

solvent

time (h)

1 2 3 4 5 6 7 8 9 10 11 12

VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(OEt)3 VO(acac)2 VO(acac)2 VO(acac)2 VO(Oi-Pr)3

10 7.5 3 7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5

toluene toluene toluene CHCl3 CH2Cl2 EtOAc CH3CN acetone toluene CH2Cl2 EtOAc toluene

24 24 3 9.5 24 24 24 24 6 6 24 24

Complexation time was 24 h.

epoxide 4a yield eeb (%) (%) 60 86 62 86 86 38 83 80 78 84 64 85 40 72 20 68 84 89 81 87 62 83 65 87

recov. 3a (%) 31 24 0 4 8 20 35 63 7 5 21 26

b

Determined by HPLC.

The vanadium/ligand ratio for the best asymmetric induction was examined via the reactions described in entries

1–3. Generally, one hydroxamic acid group (C=O–NOH) serves as one bidentate ligand using two oxygen atoms of 5 ACS Paragon Plus Environment

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carbonyl and hydroxyl groups.

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Because BBHA 2a has two hydroxamic acids and might be potentially tetradendate,

we examined the optimum molar amount of BBHA for 5 mol% of VO(OEt)3 (entries 1–3). The use of 10 mol% of 2a (potentially 20 mol% of coordination sites for 5 mol% of VO(OEt)3) and 7.5 mol% of 2a (potentially 15 mol% of coordination sites for 5 mol% of VO(OEt)3) gave better asymmetric induction of 86% ee (entries 1 and 2) than the quantities used in entry 3.

Allylic alcohol 3a was recovered in entries 1 and 2; thus, the reaction proceeded more

slowly in the cases of entries 1 and 2 than in the case of entry 3.

The vanadium excess condition in entry 3,

VO(OEt)3 5 mol% and BBHA 3 mol% (potentially 6 mol% of coordination sites), appeared to produce ligand-free vanadium species, which resulted in racemic epoxy alcohol 4a with improved yield and decreased enantioselectivity. We therefore chose the best ratio of 7.5 mol% BBHA for 5 mol% of vanadium.

Next, the solvent effect was examined using an excess–ligand condition: 5 mol% of VO(OEt)3 and 7.5 mol% of BBHA 2a. The epoxidation proceeded rapidly in CHCl3 and CH2Cl2, moderately in toluene and EtOAc, and slowly in acetonitrile and acetone (entries 4–8). A considerable amount of allylic alcohol 3a was recovered from the reactions in EtOAc, acetonitrile, and acetone. The best enantioselectivity was observed in toluene in the reaction

involving VO(OEt)3 (entries 2 and 4–7). involving VO(acac)2 (entries 9–11).

A similar tendency was observed in the solvent screening reaction

VO(acac)2 is an inexpensive, air-stable, and easy-to-handle solid reagent.

Toluene was also the best solvent for the combination of 2a and VO(acac)2. A comparison of the vanadium compounds revealed that VO(acac)2 exhibited slightly better enantioselectivity than VO(OEt)3 or VO(Oi-Pr)3 (entries 2, 9, and 12). Further optimization of reaction conditions was conducted with 5 mol% of VO(acac)2 and 7.5 mol%

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of BBHA 2a in toluene.

The complexation time, oxidant, concentration, and equivalents of TBHP were examined;

the results are summarized in Table 2.

Table 2. Optimization of the Complexation Time, Oxidant, Reaction Temperature, and Equivalents of TBHP

Ph

OH

Bn N OH

5 mol% VO(acac)2 7.5 mol% (S)-BBHA 2a X equiv Oxidant

O O Ph

toluene (Y mol/L) temp, time

3a

O

OH

N OH Bn

(2R,3R)-4a

(S)-BBHA 2a

entry

complexation time (h)

oxidant

conc. (Y mol/L)

oxidant (X equiv)

reaction temp. (°C)

reaction time (h)

1 2 3 4 5 6 7 8 9 10 11 12

24 6 3 3 3 3 3 3 3 3 3 3b

TBHP (in water) TBHP (in water) TBHP (in water) TBHP (in nonane) CHP TBHP (in water) TBHP (in water) TBHP (in water) TBHP (in water) TBHP (in water)c TBHP (in water) TBHP (in water)

0.1 0.1 0.1 0.1 0.1 0.1 0.25 0.5 1.0 1.0 0.1 0.1

1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 3.0 3.0 3.0

20 20 20 20 20 0 0 0 0 0 0 0

6 4 4 24 24 48 48 48 48 48 48 24

a

epoxide 4a yield (%) 84 88 88 84 67 80 80 77 81 86 87 93

eea (%) 89 89 89 89 83 92 90 90 93 91 92 89

recov 3a (%) 7 4 1 1 27 10 17 21 17 5 2 0

Determined by HPLC. b5 mol% VO(acac)2 and 5.5 mol% BBHA 2a was used. During the complexation process in toluene at 20 °C for 24 h (entry 1), dark-green toluene-insoluble VO(acac)2

became a dark-purple solution with BBHA 2a.

Shorter complexation time was examined for convenience of

epoxidation. Nearly the same change in color was observed at 3 h (entry 3), and the ee of the epoxide 4a was the

same as for 24 h.

Three hours was sufficient for the complexation of 2a to obtain the best enantioselectivity in

toluene solution at 20 °C (entries 1−3).

Hydroperoxide species were investigated (entries 3−5) under these

complexation conditions. The use of a water solution or nonane solution of TBHP gave the same ee of 89%. The 7 ACS Paragon Plus Environment

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use of the nonane solution of TBHP required a longer reaction time of 24 h for the consumption of allylic alcohol 3a (entry 4).

The epoxidation employing cumene hydroperoxide (CHP) in aromatic hydrocarbon proceeded more

slowly, and the enantioselectivity slightly decreased (entry 5).

Compared to the epoxidation at 20 °C (entry 3),

reaction at the lower temperature of 0 °C improved the enantioselectivity to 92% ee (entry 6). Next, the substrate

concentration and equivalents of TBHP were examined.

Higher substrate concentrations (0.1 vs. 0.25−1 mol/L) did

not improve the yields (entries 6 vs. 7−9), whereas excess TBHP (3 equiv) slightly improved the yields (entries 9−10).

Under TBHP (3 equiv) conditions, no influence of substrate concentration on the yield and enantioselectivity was

observed (entries 10 and 11).

Based on the best epoxidation condition in entry 11 (87% yield, 92% ee), more

ligand-efficient condition was re-examined.

The molar ratio of VO(acac)2/BBHA 2a was changed from 5/7.5 to

5/5.5. Unfortunately, enantioselectivity was decreased to 89% ee, whereas the yield was increased to 93% in 24 h.

The substrate scope of the epoxidation was examined under the optimized reaction conditions (Table 2, entry11)

using BBHA 2a with a complexation time of 3 h.

by chiral-stationary-phase HPLC analysis.

The results are summarized in Table 3. The ee was determined

For the HPLC analysis of aliphatic epoxy alcohols 4f–4k, the epoxy

alcohols were converted into benzoate derivatives. The absolute stereochemistry of the epoxide was determined by

comparison of the chiroptical properties with the literature data.

Table 3. Epoxidation of Various Allylic Alcohols Using 5 mol% of VO(acac)2 and 7.5 mol% of BBHA 2

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R N OH

5 mol% VO(acac)2 7.5 mol% (S)-BBHA 2 3 equiv TBHP-w

R1 R2

OH

R1 R2

toluene (0.1 mol/L) 0 oC

R3 3

O O (R) R3

O

OH

N OH R

4

R = Bn: (S)-BBHA 2a R = Ph: (S)-BBHA 2b

epoxide 4 entry

ligand

time configurationa

a

yield (%)

ee (%)b

1 2

2a 2b

2d 2d

4a

87 84

92 16

2 3

3

2a

4d

4b

95

87

1

4

2a

4d

4c

29

82

39

5

2a

4d

4d

18

89

70

6 7

2a 2b

6d 5d

4e

20 26

21 11c

0 14

8

2a

3d

4f

89

98d

0

9

2a

3d

4g

95

84d

0

10

2a

1d

4h

60

80d

0

11

2a

1d

4i

52

83d

0

12

2a

5d

4j

75

80d

8

13

2a

5d

4k

86

87d

14

Determined by comparison of the chiroptical property with the literature data.

product was (S)-4e.

recov. 3 (%)

d

b

Deteremined by HPLC.

c

Major

Determined by HPLC after benzoylation or m-toluoylation of the isolated products.

The epoxidation of trisubstituted allylic alcohols proceeded faster than the epoxidation of disubstituted allylic 9 ACS Paragon Plus Environment

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alcohols (entries 1, 3 vs. entries 4−6 and entries 8−11 vs. entries 12−13). Although the chemical reactivity of the

vanadium complex of BBHA 2b was almost the same as the chemical reactivity of BBHA 2a, enantioselectivity was

low for the epoxidation of 3a (entry 1−2).

In the case of the epoxidation of geminal substituted allylic alcohol 3e,

the opposite enantiomer of (S)-4e was obtained when BBHA 2b were used in the reaction (entries 6−7). The enantioselectivity of the epoxidation was better in the case of the reaction of trisubstituted allylic alcohols than in the

case of disubstituted allylic alcohols (entries 1, 3 vs. entries 4−6).

In the reaction of disubstituted allylic alcohols,

enantioselectivity of the epoxidation increased in the order geminal < trans < cis with respect to the geometry of the

olefin moiety (entries 4−6 and 12−13). Epoxidation of a bulky trisubstituted allylic alcohol, geraniol (3f), showed excellent enantioselectivity and gave epoxide 4f in 98% ee (entry 8).17

In the epoxidation of geraniol (3f) and nerol

(3g), allylic alcohol moieties were predominantly epoxidized over the trisubstituted alkene moieties, and no

over-oxidized products were obtained (entries 8 and 9). The epoxidation of low-molecular-weight allylic alcohol 3h

proceeded with good enantioselectivity to give epoxy alcohol 4h (entry 10).

The use of (S)-configured BBHA 2a

gave (2R)-epoxy alcohols as the major enantiomers in all cases. CONCLUSIONS

We observed that binaphthyl-based BBHA 2a was an effective ligand for the vanadium-catalyzed asymmetric epoxidation of allylic alcohols.

The (S)-BBHA ligands were easily synthesized by the one-pot, three-step procedure

from (S)-1,1′-binaphthyl-2,2′-dicarboxylic acid.

The combination of the stable and inexpensive VO(acac)2 and a

TBHP water solution as the oxidant in toluene gave the epoxy alcohols in the best enantioselectivities.

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The reaction

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proceeded faster for trisubstituted allylic alcohols than for disubstituted allylic alcohols.

The enantioselectivity was

better for trisubstituted allylic alcohols. The stereochemistry of the epoxy alcohols corresponded to (2R)-structures

in all cases when (S)-BBHA 2a was used for the epoxidation.

Further study of the coordination structure and the

mechanisms of asymmetric induction and further development of other BBHAs are in progress. EXPERIMENTAL SECTION

General Experimental Methods.

The epoxidations were conducted under air without anhydrous conditions.

Reactions for the syntheses of BBHA ligands and allylic alcohols and for the benzoylation of epoxy alcohols were

conducted in anhydrous conditions under argon atmosphere. All solvents and reagents were used as received.

1

H

NMR and 13C{1H} NMR spectra were collected with spectrometers operating at 300 or 500 MHz for proton nuclei in

the solvents indicated. 13

1

H chemical shifts are reported in δ ppm with tetramethylsilane (TMS) as an internal standard.

C{1H} chemical shifts are reported relative to the central peak of CDCl3 (77.0 ppm) or DMSO-d6 (39.52).

spectra were collected using an FT-IR spectrometer.

Infrared

Melting points were measured on a hot-plate melting-point

apparatus and are uncorrected. High-resolution mass spectra were obtained on a double-focusing high-resolution

magnetic-sector mass analyzer operating in a fast atom bombardment (FAB) mode or an electron impact (EI) mode.

Optical rotation was measured on a polarimeter.

µm, spherical) or alumina (activity III).

Chromatographic purifications were performed on silica gel (40–50

The ee of the products was determined by chiral-stationary-phase HPLC on

a chromatograph equipped with a Daicel CHIRALCEL OD-H or a CHIRALCEL OB-H column. (Z)-3-Phenyl-2-propen-1-ol18

(cis-cinnamyl

alcohol)

(3d),

2-phenyl-2-propen-1-ol19

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(3e),

and

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1-cyclohexenylmethanol20 (3i) were synthesized according to methods reported in the literature.

Synthesis

of

BBHA 2a

and

2b.

N-Benzyl-O-(trimethylsilyl)hydroxylamine

To

a

solution

of

N-benzylhydroxylamine hydrochloride (2.82 g, 17.5 mmol), DMAP (109 mg, 877 µmol), and triethylamine (29.2 mL, 210 mmol) in CH2Cl2 (175 mL) was added TMSCl (7.97 mL, 63.1 mmol) at 0 °C. The mixture was gradually warmed to room temperature and stirred for 18 h. Saturated aqueous NaHCO3 was added, and the mixture was extracted with CH2Cl2 (100 mL × 3). MgSO4, and filtered.

The combined organic layer was washed with sat. NaCl (100 mL), dried over

The filtrate was concentrated, and the residue was purified by bulb-to-bulb distillation (160 °C,

11-12 Pa) to give a colorless oil (3.26 g, 94%): 1H NMR (300 MHz, CDCl3) δ: 7.36–7.26 (5H, m), 5.21 (1H, bs), 4.01 (2H, s), 0.11 (9H, s);21 IR (neat) cm−1: 3255 (m), 2958 (m), 1604 (m), 1249 (s), 880 (m), 843 (m), 749 (m), 698 (m); EI-MS (70 eV) m/z (relative intensity): 195 (M+, 76), 180 (22), 151 (12), 102 (20), 91 (100), 75 (46).

N-Phenyl-O-(trimethylsilyl)hydroxylamine

To a solution of N-phenylhydroxylamine

(2.09 g, 19.2 mmol),

DMAP (104 mg, 852 µmol), and triethylamine (11.4 mL, 82.0 mmol) in CH2Cl2 (110 mL) was added TMSCl (5.56 mL, 44.0 mmol) at −20 °C. The mixture was gradually warmed to room temperature and stirred for 30 h. Saturated

aqueous NaHCO3 was added, and the mixture was extracted with n-hexane/Et2O = 1:2 (150 mL × 3). The combined organic layer was washed with sat. NaCl (100 mL), dried over MgSO4, and filtered.

The filtrate was concentrated

under reduced pressure at a temperature below 15 °C, and the residue was dried under vacuum.

The crude product

was then used without further purification.

(S)-N,N′-Dibenzyl-1,1′-binaphtyl-2,2′-biscarbohydroxamic

acid

(2a)

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To

a

solution

of

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(S)-1,1′-binaphthyl-2,2′-dicarboxylic acid 1 (1.50 g, 4.38 mmol) in CH2Cl2 (44 mL) were added oxalyl chloride (3.82 mL, 43.8 mmol) and DMF (100 µL) at 0 °C.

The mixture was gradually warmed to room temperature.

After gas

generation ceased (4 h), the mixture was concentrated under reduced pressure and dried under vacuum. The residue

was dissolved in CH2Cl2 (44 mL).

N-Benzyl-O-(trimethylsilyl)hydroxylamine (2.66 g, 13.7 mmol), triethylamine

(3.65 mL, 26.3 mmol), and DMAP (27.0 mg, 221 µmol) were added at 0 °C, and the mixture was brought to room temperature and stirred for 15 h.

The mixture was cooled to 0 °C, whereupon tetrabutylammonium fluoride (1 mol/L in THF, 17.5 mL, 17.5 mmol)

was added, and the resulting mixture was stirred for 3.5 h. Water (100 mL) was added, and the mixture was

extracted with CH2Cl2 (150 mL × 3).

The combined organic layer was washed with sat. NaCl (100 mL), dried over

MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 1–50% EtOAc/n-hexane + 15% THF) and recrystallization from n-hexane and

CHCl3 (1:1) to give 2a as colorless needles (1.58 g, 65%): Rf = 0.20 (silica gel, EtOAc/n-hexane/THF = 1:4:1); mp 199–202 °C; 1H NMR (500 MHz, DMSO-d6, 80°C) δ: 9.96 (2H, s), 8.10 (2H, d, J = 8.6 Hz), 8.02 (2H, d, J = 8.3 Hz), 7.60 (2H, d, J = 8.6 Hz), 7.51 (2H, ddd, J = 8.3, 7.0, 1.2 Hz), 7.26 (2H, ddd, J = 8.6, 7.1, 1.3 Hz), 7.17 (2H, d, J = 8.6

Hz), 7.14 (2H, d, J = 7.4 Hz), 7.12–7.06 (4H, m), 6.71 (4H, br), 4.58 (2H, d, J = 15.6 Hz), 4.51 (2H, d, J = 15.6 Hz); 13

C{1H} NMR (125 MHz, DMSO-d6, 80°C) δ: 168.4, 135.5, 133.8, 132.6, 132.3, 131.9, 127.6, 127.4, 127.3, 126.8,

126.7, 126.4, 126.3, 125.9, 123.7, 51.2; IR (KBr) cm−1: 3198 (br), 2905 (br), 1609 (s), 1481 (s), 1445 (m), 1421 (m), 1348 (s), 1245 (s), 1147 (s), 819 (s), 755 (s), 628 (m), 488 (m); EI-MS (70 eV) m/z (relative intensity): 552 (M+, 75),

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Page 14 of 30

430 (78), 281 (84), 252 (47), 91 (100); HRMS (EI) m/z: M+ Calcd for C36H28N2O4 552.2049; Found 552.2054; Anal. Calcd for C36H28N2O4: C, 78.24; H, 5.11; N, 5.07. Found: C, 78.14; H, 5.37; N, 5.07; [α]D21 −117 (c 0.496, CHCl3). (S)-N,N′-Diphenyl-1,1′-binaphtyl-2,2′-biscarbohydroxamic

acid

(2b)

To

a

solution

of

(S)-1,1′-binaphthyl-2,2′-dicarboxylic acid 1 (1.00 g, 2.92 mmol) in CH2Cl2 (30 mL) was added oxalyl chloride (2.50 mL, 29.2 mmol) and DMF (100 µL) at 0 °C.

The mixture was gradually warmed to room temperature. After gas

generation ceased (1.5 h), the mixture was concentrated under reduced pressure, and dried under vacuum. The

residue was dissolved in CH2Cl2 (30 mL).

N-Phenyl-O-(trimethylsilyl)hydroxylamine (1.59 g, 8.76 mmol),

triethylamine (2.43 mL, 17.5 mmol), and DMAP (22.2 mg, 182 µmol) were added at 0 °C and the resulting mixture was brought to room temperature and stirred for 20 h.

The mixture was cooled to 0 °C, whereupon

tetrabutylammonium fluoride (1 mol/L in THF, 11.7 mL, 11.7 mmol) was added, and the resulting mixture was stirred

for 3.5 h.

Water (100 mL) was added, and the mixture was extracted with CH2Cl2 (150 mL × 3).

organic layer was washed with sat. NaCl (100 mL), dried over MgSO4, and filtered. under reduced pressure.

The combined

The filtrate was concentrated

The crude product was purified by column chromatography (silica gel, 2–50%

EtOAc/n-hexane + 15% THF) and recrystallization from n-hexane and CH2Cl2 (2:1) to give 2b as colorless prisms (828 mg, 54%): Rf = 0.16 (silica gel, EtOAc/n-hexane/THF = 1:4:1); mp 119–123 °C; 1H NMR (500 MHz, DMSO-d6, 80 °C) δ: 10.41 (2H, s), 8.03 (2H, d, J = 8.6 Hz), 7.98 (2H, d, J = 8.3 Hz), 7.69 (2H, d, J = 8.6 Hz), 7.52 (2H, ddd, J = 8.0, 6.8, 1.3 Hz), 7.32 (2H, ddd, J = 8.3, 6.7, 1.2 Hz), 7.25–7.16 (10H, m), 7.11–7.06 (2H, m); 13C{1H} NMR (125

MHz, DMSO-d6, 80°C) δ: 167.9, 140.5, 134.0, 132.5, 132.3, 132.1, 127.8, 127.8, 127.3, 126.9, 126.3, 125.8, 125.4,

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The Journal of Organic Chemistry

123.9, 121.5; IR (KBr) cm−1: 3149 (br), 3065 (br), 2918 (br), 2856 (Br), 1617 (s), 1589 (s), 1490 (s), 1389 (m), 828 (m), 754 (m), 680 (m); EI-MS (70 eV) m/z (relative intensity): 524 (M+, 2), 492 (12), 416 (13), 400 (14), 372 (23), 325 (11), 281 (100), 252 (40); HRMS (EI) m/z: M+ Calcd for C36H28N2O4 552.2049; Found 552.2054; Anal. Calcd for C34H24N2O4: C, 77.85; H, 4.61; N, 5.34. Found: C, 77.71; H, 4.68; N, 5.21; [α]D21 +12.1 (c 0.444, CHCl3). Synthesis

of

Allylic

Alcohols.

(E)-2,3-Diphenyl-2-propen-1-ol

(3b)22

A

mixture

of

(E)-2,3-diphenyl-2-propennoic acid (3.02 g, 13.4 mmol) and powdered KOH (1.24 g, 18.7 mmol) in DMSO (40 mL)

was stirred at room temperature for 1 h.

The mixture was cooled to 0 °C, whereupon MeI (1.25 mL, 20.1 mmol) was

added, and the resulting mixture was stirred at room temperature for 42 h. Water (100 mL) was added, and the

mixture was extracted with n-hexane/EtOAc (1:1) (100 mL × 3). The combined organic layer was washed with

water (100 mL × 3), dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0–4% EtOAc/n-hexane) to give methyl (E)-2,3-diphenyl-2-propennoate (2.97 g, 92%) as a colorless solid: Rf = 0.22 (silica gel, EtOAc/n-hexane = 1:40); 1H NMR (300 MHz, CDCl3) δ: 7.85 (1H, s), 7.40–7.33 (3H, m), 7.23–7.12 (5H, m), 7.03 (2H, d, J = 5.5 Hz), 3.79 (3H, s).

To a solution of (E)-2,3-diphenyl-2-propennoate (2.67 g, 11.2 mmol) in Et2O (22 mL) was added DIBAL solution (0.98 mol/L in hexanes, 25.2 mL, 46.2 mmol) at 0 °C over 20 min.

and stirred for 4 h.

brine (50 mL).

The mixture was warmed to room temperature

The mixture was then re-cooled to 0 °C, and water (100 mL) was carefully added, followed by

The white solid that formed was dissolved by the addition of 2 mol/L aqueous HCl. The resulting

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mixture was extracted with Et2O (150 mL × 3).

Page 16 of 30

The combined organic layer was washed with brine (100 mL), dried

over MgSO4, and filtered. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 5–32% EtOAc/n-hexane) to give allylic alcohol 3b (2.13 g, 90%) as a colorless oil: Rf = 0.20 (silica gel, EtOAc/n-hexane = 1:4); 1H NMR (300 MHz, CDCl3) δ: 7.37–7.28 (3H, m), 7.28–7.19, (2H, m), 7.16–7.06 (3H, m), 7.20–6.94 (2H, m), 6.69 (1H, s), 4.47 (2H, d, J = 2.9 Hz), 1.64 (1H, br); EI-MS (70 eV) m/z (relative intensity): 210 (M+, 100), 191 (13), 178 (40), 165 (14), 105 (69), 91 (33), 77 (11); IR (KBr) cm−1: 3262 (m),

1445 (m), 1091 (m), 1071 (m), 1004 (m), 916 (m), 694 (m).

Typical Procedure for the Asymmetric Epoxidation: Epoxidation of 3a (Table 3, Entry 1). A mixture of

VO(acac)2 (6.62 mg, 25.0 µmol) and BBHA 2a (20.7 mg, 37.5 µmol) in toluene (5.00 mL) was stirred at 20 °C for 3 h. To the resulting dark-purple solution, TBHP in water (70 %, 206 µL, 1.5 mmol, 3.0 equiv) was added at 0 °C; the

resulting mixture was stirred for 10 min. monitored by TLC.

Allylic alcohol 3a (74.6 mg, 500 µmol) was added, and the reaction was

Saturated aqueous Na2SO3 solution was added. The mixture was stirred for 30 min and

extracted with Et2O or EtOAc (5 mL × 5). filtrate was concentrated under vacuum.

The combined organic layer was dried over MgSO4 and filtered. The The crude product was purified by column chromatography (silica gel,

5−40% EtOAc/n-hexane) to give epoxy alcohol 4a as colorless needles (72.3 mg, 87%). HPLC analysis of 4a

indicated 92% ee. To isolate the volatile aliphatic epoxy alcohols (4h, 4j, 4k), a partially concentrated solution of crude epoxy alcohols, mostly in toluene, was charged directly to the column for chromatography.

was used instead of silica gel for the purification of epoxy alcohols 4d, 4f, 4g, 4h, 4i, 4j, and 4k.

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Al2O3 (activity III)

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The Journal of Organic Chemistry

Benzoylation and m-Toluoylation of Aliphatic Epoxy Alcohols (4f−4k).

To a CH2Cl2 (0.25 mol/L) solution of

epoxy alcohol 4f−4k (1 equiv), DMAP (2 mol%), and NEt3 (3 equiv) was added RCOCl (1.2 equiv) at 0 °C. The mixture was gradually warmed to room temperature and stirred for 5 h.

the organic layer was extracted with CH2Cl2.

Saturated aqueous NaHCO3 was added, and

The extracts were dried over MgSO4, filtered, and concentrated. The

crude ester was purified by column chromatography (silica gel, EtOAc/n-hexane or EtOAc/n-hexane/CH2Cl2) to give esters of 4f−4h-benzoyl and 4i−4k-toluoyl.

(2R,3R)-(2-Methyl-3-phenyloxiran-2-yl)methanol (4a)

Purified by silica gel column chromatography (5–40%

EtOAc/n-hexane) to give 72.3 mg (87%) of colorless needles: mp 50–52 °C (lit.23 52–53 °C); Rf = 0.13 (silica gel, EtOAc/n-hexane = 1:4); 1H NMR (500 MHz, CDCl3) δ: 7.37–7.27 (5H, m), 4.21 (1H, s), 3.85 (1H, dd, J = 12.6, 2.8 Hz), 3.75 (1H, dd, J = 12.6, 8.2 Hz), 2.04 (1H, br), 1.09 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) δ: 135.6, 128.9, 127.6, 126.4, 65.0, 63.6, 60.2, 13.4; IR (KBr) cm−1: 3424 (m), 1451 (m), 1094 (m), 1070 (m), 851 (m), 740 (m), 699 (m), 554 (m), 507 (m); EI-MS (70 eV) m/z (relative intensity): 164 (M+, 7), 145 (10), 131 (22), 107 (100), 90 (71), 79 (39), 77 (25), 58 (13); HRMS (EI) m/z: M+ Calcd for C10H12O2 164.0837; Found 164.0843; [α]D25 +13.6 (c 1.28, CHCl3, 92% ee), (lit.16 [α]D25 −16.9 [c 2.0, CHCl3, (2S,3S)-epoxide, >98% ee]); HPLC conditions: OD-H, n-hexane/2-propanol = 95/5, 0.4 mL/min, 210 nm, 28.2 min (2S,3S), minor, 36.0 min (2R,3R), major.8a

(2R,3R)-(2,3-Diphenyloxiran-2-yl)methanol (4b)

Purified by silica gel column chromatography (4–40%

EtOAc/n-hexane) to give 107.3 mg (95%) of colorless solid: mp 66–69 °C (lit.23 115–116 °C); Rf = 0.13 (silica gel, EtOAc/n-hexane = 1:6); 1H NMR (500 MHz, CDCl3) δ: 7.23–7.15 (5H, m), 7.12–7.09 (3H, m), 7.05–7.01 (2H, m),

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4.51 (1H, s), 4.06–4.00 (2H, m), 2.06 (1H, t, J = 6.7 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ: 134.7, 134.4, 128.3, 127.8, 127.71, 127.66, 127.5, 126.6, 69.1, 65.0, 60.8; IR (KBr) cm−1: 3401 (m), 1496 (m), 1455 (m), 1093 (m), 1036 (m), 1004 (m), 908 (m), 754 (m), 700 (m); EI-MS (70 eV) m/z (relative intensity): 226 (M+, 6), 195 (26), 167 (51), 152 (9), 120 (100), 105 (27), 91 (72), 77 (22); HRMS (EI) m/z: M+ Calcd for C15H14O2 226.0994; Found 226.0992; [α]D28 –65.4 (c 1.97, CHCl3, 87% ee), [α]D18 –55.6 (c 1.08, CH2Cl2, 87% ee), [lit.2a (+)-(2S,3S)-epoxide (>95% ee) was reported.]; HPLC conditions: OD-H, n-hexane/2-propanol= 95/5, 1 mL/min, 210 nm, 13.5 min (2S,3S), minor, 15.7 min (2R,3R), major.8a,23

(2R,3R)-(3-Phenyloxiran-2-yl)methanol (4c)

Purified by silica gel column chromatography (5–40%

EtOAc/n-hexane) to give 21.9 mg (29%) of colorless oil: Rf = 0.15 (silica gel, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 7.37–7.25 (5H, m), 4.04 (1H, ddd, J = 12.8, 5.2, 2.5 Hz), 3.92 (1H, d, J = 2.2 Hz), 3.79 (1H, dd, J = 12.8, 7.6, 4.0 Hz), 3.22 (1H, dt, J = 4.0, 2.0 Hz), 2.09 (1H, dd, J = 7.7, 5.5 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ: 136.7, 128.5, 128.3, 125.7, 62.4, 61.3, 55.6; IR (KBr) cm−1: 3439 (m), 1464 (m), 1398 (m), 1069 (m), 929 (m), 768 (m), 700 (m); EI-MS (70 eV) m/z (relative intensity): 150 (M+, 15), 132 (30), 119 (27), 107 (100), 91 (95), 90 (84), 79 (41); HRMS (EI) m/z: M+ Calcd for C9H10O2 150.0681; Found 150.0680; [α]D24 +37.2 (c 0.340, CHCl3, 82% ee), (lit.16 [α]D25 −49.6 [c 2.4, CHCl3, (2S,3S)-epoxide, 98% ee]); HPLC conditions: OD-H, n-hexane/2-propanol= 90/10, 0.5 mL/min, 210 nm, 24.5 min (2S,3S), minor, 27.1 min (2R,3R), major.8a

(2R,3S)-(3-Phenyloxiran-2-yl)methanol

(4d)

Purified

by

Al2O3

column

chromatography

(10–100%

EtOAc/n-hexane) to give 13.9 mg (18%) of colorless oil: Rf = 0.15 (silica gel, EtOAc/n-hexane = 1:3), 0.20 (Al2O3,

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The Journal of Organic Chemistry

EtOAc/n-hexane = 1:1); 1H NMR (500 MHz, CDCl3) δ: 7.37–7.25 (5H, m), 4.19 (1H, d, J = 4.3 Hz), 3.57–3.52 (1H, m), 3.48–3.42 (2H, m), 1.57 (1H, br);

13

C{1H} NMR (125 MHz, CDCl3) δ: 134.7, 128.3, 127.9, 126.2, 60.5, 58.5,

57.0; IR (neat) cm−1: 3391 (br), 1496 (m), 1454 (s), 1041 (s), 894 (m), 745 (S), 700 (S); EI-MS (70 eV) m/z (relative intensity): 150 (M+, 4), 132 (31), 119 (28), 107 (100), 90 (85), 79 (41), 51 (11); HRMS (EI) m/z: M+ Calcd for C9H10O2 150.0681; Found 150.0678; [α]D21 +35.0 (c 0.344, CHCl3, 89% ee), (lit.24 [α]D25 −50 [c 3.3, CHCl3, (2S,3R)-epoxide, 78% ee]); HPLC conditions: OD-H, n-hexane/2-propanol= 90/10, 0.5 mL/min, 210 nm, 19.5 min (2R,3S), major, 24.8 min (2S,3R), minor.8a

(R)-(2-Phenyloxiran-2-yl)methanol (4e) Purified by silica gel column chromatography (5–40% EtOAc/n-hexane) to give 17.4 mg (20%) of colorless oil: TLC Rf = 0.14 (silica gel, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 7.40–7.30 (5H, m), 4.10 (1H, d, J = 12.5 Hz), 4.00 (1H, d, J = 12.5 Hz), 3.26 (1H, d, J = 5.5 Hz), 2.82 (1H, d, J = 5.5 Hz), 2.12 (1H, br); 13C{1H} NMR (125 MHz, CDCl3) δ: 137.3, 128.5, 128.1, 126.0, 63.1, 60.4, 52.5; IR (neat) cm−1: 3420 (br, s), 2926 (m), 1496 (m), 1448 (m), 1044 (m), 1024 (m), 761 (s), 699 (s); EI-MS (70 eV) m/z (relative intensity): 150 (M+, 3), 120 (92), 105 (23), 91 (100), 77 (20); HRMS (FAB) m/z: [M+H]+ Calcd for C9H11O2, 151.0759; Found, 151.0761; [α]D22 +5.19 (c 0.233, CHCl3, 21% ee), (lit.25 [α]D25 +27.4 [c 1.3, CHCl3, (2R)-epoxide, 77% ee]); HPLC conditions: OD-H, n-hexane/2-propanol= 90/10, 1 mL/min, 210 nm, 9.4 min (2S), minor, 11.8 min (2R), major.8a

(2R,3R)-Geraniol-2,3-epoxide (4f) Purified by Al2O3 column chromatography (7–60% EtOAc/n-hexane) to give 76.5 mg (89%) of colorless oil: Rf = 0.13 (Al2O3, EtOAc/n-hexane = 3:7), 0.20 (silica gel, EtOAc/n-hexane = 1:3); 1H

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Page 20 of 30

NMR (500 MHz, CDCl3) δ: 5.11–5.05 (1H, m), 3.83 (1H, ddd, J = 11.9, 7.8, 4.6 Hz), 3.68 (1H, ddd, J = 11.6, 6.7, 4.6 Hz), 2.98 (1H, dd, J = 6.7, 4.3 Hz), 2.09 (2H, q, J = 7.6 Hz), 1.94 (1H, dd, J = 7.0, 4.9 Hz), 1.74–1.65 (1H, m), 1.69 (3H, d, J = 0.9 Hz), 1.61 (3H, s), 1.48 (1H, ddd, J = 13.8, 9.2, 7.1 Hz), 1.30 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) δ: 132.1, 123.3, 62.9, 61.4, 61.1, 38.5, 25.6, 23.7, 17.6, 16.7; IR (neat) cm−1: 3419 (br, s), 2968 (s), 1451 (s), 1384 (s), 1036 (s), 865 (m); EI-MS (70 eV) m/z (relative intensity): 170 (M+, 1), 152 (3), 139 (5), 121 (7), 109 (100), 95 (26), 82 (46), 69 (67); HRMS (EI) m/z: M+ Calcd for C10H18O2 170.1307; Found 170.1303; [α]D25 +4.93 (c 1.44, CHCl3, 98% ee), (lit.16 [α]D25 –5.3 [c 3.0, CHCl3, (2S,3S)-epoxide, 91% ee]). (2R,3R)-2,3-Epoxygeranyl benzoate (4f-benzoyl)

Purified by silica gel column chromatography (1–10%

EtOAc/n-hexane) to give 99.6 mg (86% based on 422 µmol 4f) of colorless oil: Rf = 0.27 (silica gel, EtOAc/n-hexane = 1:15); 1H NMR (500 MHz, CDCl3) δ: 8.11–8.07 (2H, m), 7.59–7.56 (1H, m), 7.47–7.42 (2H, m), 5.15–5.09 (1H, m), 4.59 (1H, dd, J = 12.2, 4.5 Hz), 4.27 (1H, dd, J = 11.9, 7.1 Hz), 3.13 (1H, dd, J = 6.7, 4.0 Hz), 2.23–2.09 (2H, m), 1.75–1.67 (1H, m), 1.70 (3H, d, J = 0.9 Hz), 1.62 (3H, s) 1.60–1.53 (1H, m), 1.38 (3H, s); 13C{1H} NMR (125 MHz,

CDCl3) δ: 166.4, 133.1, 132.5, 129.8, 129.7, 128.4, 123.2, 63.7, 61.0, 60.8, 33.3, 25.7, 24.2, 22.0, 17.6; IR (neat) cm−1: 2967 (s), 1723 (s), 1451 (s), 1272 (s), 1109 (m), 712 (m); EI-MS (70 eV) m/z (relative intensity): 274 (M+, 1), 256 (1), 192 (14), 134 (9), 105 (100), 77 (18); HRMS (EI) m/z: M+ Calcd for C17H22O3 274.1569; Found 274.1572; [α]D25 +15.1 (c 1.71, CHCl3, 98% ee), (lit.26 [α]D27 –13.8 [c 1.0, CHCl3, (2S,3S)-epoxide, 99% ee]); HPLC conditions: OD-H, n-hexane/2-propanol= 99/1, 1 mL/min, 254 nm, 10.3 min (2R,3R), major, 15.7 min (2S,3S), minor.

(2R,3S)-Nerol-2,3-epoxide (4g) Purified by Al2O3 column chromatography (7–60% EtOAc/n-hexane) to give 80.5

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The Journal of Organic Chemistry

mg (95%) of colorless oil: Rf = 0.16 (Al2O3, EtOAc/n-hexane = 3:7), 0.21 (silica gel, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 5.12–5.06 (1H, m), 3.84–3.77 (1H, m), 3.67–3.62 (1H, m), 2.97 (1H, dd, J = 7.0, 4.3 Hz), 2.40 (1H, br), 2.18–2.02 (2H, m),1.69 (3H, s), 1.70–1.63 (1H, m), 1.62 (3H, s), 1.48 (1H, ddd, J = 13.7, 10.1, 7.0 Hz), 1.34 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) δ: 132.4, 123.3, 64.3, 61.5, 61.2, 33.1, 25.6, 24.1, 22.1, 17.5; IR (neat) cm−1: 3419 (br, s), 2968 (s), 1450 (s), 1380 (s), 1034 (s), 865 (m); FAB-MS (glycerol) m/z: 171 [M+H]+; HRMS (FAB) m/z: [M+H]+ Calcd for C10H19O2 171.1385; Found 171.1387; [α]D25 +17.8 (c 1.42, CHCl3, 84% ee), (lit.27 [α]D +15.4 [c 3.3, CHCl3, (2R,3S)-epoxide, 70% ee]). (2R,3S)-2,3-Epoxyneryl benzoate (4g-benzoyl)

Purified by silica gel column chromatography (1–10%

EtOAc/n-hexane) to give 97.3 mg (88% based on 402 µmol 4g) of colorless oil: Rf = 0.29 (silica gel, EtOAc/n-hexane = 1:15); 1H NMR (500 MHz, CDCl3) δ: 8.09–8.06 (2H, m), 7.59–7.55 (1H, m), 7.46–7.43 (2H, m), 5.15–5.10 (1H, m), 4.59 (1H, dd, J = 11.9, 4.0 Hz), 4.28 (1H, dd, J = 11.9, 7.1 Hz), 3.13 (1H, dd, J = 8.0, 5.3 Hz), 2.23–2.10 (2H, m), 1.73–1.65 (1H, m), 1.70 (3H, d, J = 0.9 Hz), 1.62 (3H, s), 1.59–1.53 (1H, m), 1.38 (3H, s); 13C{1H} NMR (125 MHz,

CDCl3) δ: 166.4, 133.1, 132.5, 129.8, 129.7, 128.4, 123.2, 63.7, 61.0, 60.8, 33.3, 25.6, 24.2, 22.0, 17.6; IR (neat) cm−1: 2967 (m), 1722 (s), 1451 (m), 1272 (s), 1109 (m), 712 (s); EI-MS (70 eV) m/z (relative intensity): 274 (M+, 0.2), 191 (5), 134 (9), 105 (100), 77 (22); HRMS (EI) m/z: M+ Calcd for C17H22O3 274.1569; Found 274.1572; [α]D26 +19.1 (c 1.25, CHCl3, 84% ee); HPLC conditions: OD-H, n-hexane/2-propanol = 99.7/0.3, 1 mL/min, 230 nm, 11.3 min (2S,3R), minor, 16.7 min (2R,3S), major.28

(2R)-(3,3-Dimethyloxiran-2-yl)methanol

(4h)

Purified

by

Al2O3

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chromatography

(8–66%

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EtOAc/n-hexane) to give 30.7 mg (60%) of colorless oil: Rf = 0.16 (Al2O3, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 3.83 (1H, dd, J = 12.2, 1.2 Hz), 3.67 (1H, dd, J = 12.2, 7.1 Hz), 2.99 (1H, dd, J = 6.7, 4.3 Hz), 2.89 (1H, br), 1.35 (3H, s), 1.31 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) δ: 63.9, 61.3, 58.8, 24.7, 18.7; IR (neat) cm−1: 3419 (br, s), 1456 (s), 1380 (s), 1033 (s), 858 (m); FAB-MS (glycerol) m/z: 103 ([M+H]+); HRMS (FAB) m/z: [M+H]+ Calcd for C5H11O2 103.0759; Found 103.0757; [α]D22 +13.0 (c 0.417, CHCl3, 80% ee), (lit.29 [α]D25 −19.4 [c 0.40, CHCl3, (2S)-epoxide, 86% ee]). (2R)-(3,3-Dimethyloxiran-2-yl)methyl benzoate (4h-benzoyl)

Purified by silica gel column chromatography

(0–4% EtOAc/n-hexane + 2% CH2Cl2) to give 40.7 mg (66% based on 300 µmol 4h) of colorless oil: Rf = 0.09 (silica gel, EtOAc/n-hexane/CH2Cl2 = 1:40:1); 1H NMR (500 MHz, CDCl3) δ: 8.09–8.06 (2H, m), 7.60–7.55 (1H, m), 7.47–7.43 (2H, m), 4.59 (1H, dd, J = 12.2, 4.3 Hz), 4.28 (1H, dd, J = 12.2, 6.7 Hz), 3.14 (1H, dd, J = 6.7, 4.3 Hz), 1.390 (3H, s), 1.387 (3H, s); 13C{1H} NMR (125 MHz, CDCl3) δ: 166.4, 133.1, 129.8, 129.7, 128.4, 63.9, 60.6, 58.2, 24.6, 19.0; IR (neat) cm−1: 2965 (m), 1722 (s), 1453 (m), 1273 (m), 1113 (m), 711 (m); FAB-MS (m-nitrobenzylalcohol) m/z: 207 ([M+H]+); HRMS (FAB) m/z: [M+H]+ Calcd for C12H15O3 207.1021; Found 207.1029; [α]D22 +22.2 (c 0.573, CHCl3, 80% ee), (lit.30 [α]D25 –22.2 [c 1.00, CHCl3, (S)-epoxide, 90% ee]); HPLC conditions: OB-H, n-hexane/2-propanol = 90/10, 1 mL/min, 230 nm, 12.5 min (2S), minor, 16.3 min (2R), major.

Purified by Al2O3 column chromatography (7–60%

(1R,6R)-7-Oxabicyclo[4.1.0]heptan-1-ylmethanol (4i)

EtOAc/n-hexane) to give 33.7 mg (52%) of colorless oil: Rf = 0.16 (Al2O3, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 3.68 (1H, d, J = 11.9 Hz), 3.59 (1H, dd, J = 12.2, 7.9 Hz), 3.26 (1H, d, J = 3.4 Hz), 1.98 (1H, dt, J =

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The Journal of Organic Chemistry

15.6, 7.5 Hz), 1.99–1.77 (3H, m), 1.74–1.66 (1H, m), 1.53–1.42 (2H, m), 1.33–1.22 (2H, m);

13

C{1H} NMR (125

MHz, CDCl3) δ: 64.5, 60.1, 55.8, 25.3, 24.4, 19.9, 19.6; IR (neat) cm−1: 3418 (s), 2937 (s), 1434 (m), 1109 (m), 1069 (m), 1034 (m), 917 (m), 835 (m); FAB-MS (glycerol) m/z: 129 ([M+H]+); HRMS (FAB) m/z: [M+H]+ Calcd for C7H13O2 129.0916; Found 129.0915; [α]D24 +9.64 (c 0.512, CHCl3, 81% ee), (lit.16 [α]D25 −22.8 [c 2.6, CHCl3, (S,S)-epoxide, 93% ee]).

(1R,6R)-7-Oxabicyclo[4.1.0]heptan-1-ylmethyl 3-methylbenzoate (4i-toluoyl)

Purified by silica gel column

chromatography (0–4% EtOAc/n-hexane + 2% CH2Cl2) to give 43.9 mg (71% based on 251 µmol 4i) of colorless oil: Rf = 0.09 (silica gel, EtOAc/n-hexane/CH2Cl2 = 1:40:1); 1H NMR (500 MHz, CDCl3) δ: 7.87–7.83 (2H, m), 7.38 (1H, d, J = 7.9 Hz), 7.33 (1H, t, J = 7.7 Hz), 4.46 (1H, d, J = 11.9 Hz), 4.18 (1H, d, J = 11.9 Hz), 3.21 (1H, d, J = 3.4 Hz), 2.41 (3H, s), 2.05–1.95 (2H, m), 1.91–1.84 (2H, m), 1.54–1.44 (2H, m), 1.36–1.23 (2H, m); 13C{1H} NMR (125 MHz,

CDCl3) δ: 166.4, 138.2, 138.9, 130.2, 129.8, 128.3, 126.9, 68.4, 57.8, 56.7, 25.5, 24.3, 21.3, 19.7, 19.5; IR (neat) cm−1: 2938 (s), 1719 (s), 1590 (m), 1436 (m), 1274 (m), 1197 (s), 1083 (m), 1001 (m), 744 (s); EI-MS (20 eV) m/z (relative intensity): 246 (M+, 0.5), 119 (100); HRMS (EI) m/z: M+ Calcd for C15H18O3 246.1256; Found 246.1254; Anal. Calcd for C15H18O3: C, 73.15; H, 7.37. Found: C, 73.23; H, 7.40; [α]D21 +11.8 (c 0.624, CHCl3) (81% ee); HPLC conditions: OB-H, n-hexane/2-propanol = 90/10, 1 mL/min, 230 nm, 9.6 min (S,S), minor, 14.2 min (R,R),

major.

(2R,3R)-(3-Propyloxiran-2-yl)methanol (4j) Purified by Al2O3 column chromatography (7–60% EtOAc/n-hexane) to give 43.9 mg (75%) of colorless oil: Rf = 0.14 (Al2O3, EtOAc/n-hexane = 3:7); 1H NMR (500 MHz, CDCl3) δ: 3.91

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(1H, d, J = 12.6 Hz), 3.63 (1H, d, J = 12.2 Hz), 2.96 (1H, td, J = 5.7, 2.4 Hz), 2.92 (1H, dt, J = 4.3, 2.4 Hz), 1.85 (1H, br), 1.58–1.42 (4H, m), 0.97 (3H, t, J = 7.2 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ: 61.7, 58.4, 55.8, 33.6, 19.2, 13.7; IR (neat) cm−1: 3419 (br, s), 2961 (s), 1665 (m), 1382 (m), 1223 (m), 1065 (m), 1045 (m), 901 (m), 854 (m); FAB-MS (glycerol) m/z: 107 ([M+H]+); HRMS (FAB) m/z: [M+H]+ Calcd for C6H13O2, 117.0916; Found, 117.0918; [α]D23 +27.0 (c 0.694, CHCl3, 80% ee), (lit.31 [α]D25 −46.6 [c 1.0, CHCl3, (2S,3S)-epoxide, 96.8% ee]). (2R,3R)-(3-Propyloxiran-2-yl)methyl

3-methylbenzoate

(4j-toluoyl)

Purified

by

silica

gel

column

chromatography (0–4% EtOAc/n-hexane + 2% CH2Cl2) to give 44.4 mg (50% based on 378 µmol 4j) of colorless oil: Rf = 0.14 (silica gel, EtOAc/n-hexane/CH2Cl2 = 1:40:1); 1H NMR (500 MHz, CDCl3) δ: 7.88 (1H, d, J = 0.7 Hz), 7.86 (1H, d, J = 7.9 Hz), 7.37 (1H, d, J = 7.7 Hz), 7.33 (1H, t, J = 7.7 Hz), 4.59 (1H, dd, J = 12.0, 3.4 Hz), 4.18 (1H, dd, J

= 12.0, 6.0 Hz), 3.10 (1H, ddd, J = 5.7, 3.4, 2.2 Hz), 2.93 (1H, td, J = 5.7, 2.2 Hz), 2.40 (3H, s), 1.62–1.42 (4H, m), 0.97 (3H, t, J = 7.3 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ: 166.4, 138.1, 133.9, 130.2, 129.6, 128.2, 126.8, 65.1, 56.5, 55.3, 33.5, 21.2, 19.1, 13.8; IR (neat) cm−1: 2960 (s), 1721 (s), 1276 (m), 1199 (m), 1106 (m), 1082 (m), 745 (m); EI-MS (70 eV) m/z (relative intensity): 234 (M+, 1), 191 (1), 136 (4), 119 (100), 91 (17); HRMS (EI) m/z: M+ Calcd for C14H18O3 234.1256; Found 234.1258; [α]D20 +31.7 (c 0.550, CHCl3, 80% ee); HPLC conditions: OB-H, n-hexane/2-propanol = 98/2, 0.5 mL/min, 230 nm, 30.4 min (2R,3R), major, 34.8 min (2S,3S), minor.8a

(2R,3S)-(3-Propyloxiran-2-yl)methanol (4k) Purified by Al2O3 column chromatography (7–60% EtOAc/n-hexane) to give 50.5 mg (86%) of colorless oil: Rf = 0.14 (Al2O3, EtOAc/n-hexane = 3:7); Rf = 0.14 (silica gel, EtOAc/n-hexane = 1:3); 1H NMR (500 MHz, CDCl3) δ: 3.85 (1H, dd, J = 12.2, 4.0 Hz), 3.67 (1H, dd, J = 12.2, 7.0

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Hz), 3.16 (1H, dt, J = 4.3, 2.1 Hz), 3.07–3.01 (1H, m), 1.59–1.41 (4H, m), 2.37 (1H, br), 0.98 (3H, t, J = 7.0 Hz); 13

C{1H} NMR (125 MHz, CDCl3) δ: 60.9, 57.1, 56.9, 29.9, 19.9, 13.8; IR (neat) cm−1: 3408 (br, s), 2962 (s), 1465 (m),

1042 (s), 914 (m), 858 (m), 829 (m), 768 (m); FAB-MS (glycerol) m/z: 117 ([M+H]+).

HRMS (FAB) m/z: [M+H]+

Calcd for C6H13O2 117.0916; Found 117.0919; [α]D22 +2.87 (c 0.757, CHCl3, 87% ee), (lit.32 [α]D21.5 −4.99 [c 3.64, CHCl3, (2S,3R)-epoxide, 85.8% ee]). (2R,3S)-(3-Propyloxiran-2-yl)methyl

3-methylbenzoate

(4k-toluoyl)

Purified

by

silica

gel

column

chromatography (0–4% EtOAc/n-hexane + 2% CH2Cl2) to give 50.9 mg (50% based on 435 µmol 4k) of colorless oil: Rf = 0.16 (EtOAc/n-hexane/CH2Cl2 = 1:40:1); 1H NMR (500 MHz, CDCl3) δ: 7.89 (1H, d, J = 0.6 Hz), 7.88 (1H, d, J = 7.6 Hz), 7.38 (1H, d, J = 7.9 Hz), 7.33 (1H, t, J = 7.6 Hz), 4.58 (1H, dd, J = 11.9, 4.3 Hz), 4.28 (1H, dd, J = 12.2,

7.0 Hz), 3.32 (1H, dt, J = 7.0, 3.5 Hz), 3.08 (1H, td, J = 6.1, 4.3 Hz), 2.41 (3H, s), 1.64–1.46 (4H, m), 1.01 (3H, t, J = 7.2 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ: 166.6, 138.2, 133.9, 130.3, 129.7, 128.3, 126.9, 63.3, 56.4, 53.8, 30.0, 21.2, 19.9, 13.9; IR (neat) cm−1: 2961 (s), 1721 (s), 1457 (m), 1278 (s), 1199 (s), 1107 (m), 1083 (m), 745 (s); EI-MS (70 eV) m/z (relative intensity): 234 (M+, 1), 119 (100), 91 (16); HRMS (EI) m/z: M+ Calcd for C14H18O3 234.1256; Found 234.1259; [α]D21 +14.2 (c 0.793, CHCl3, 87% ee); HPLC conditions: OB-H, n-hexane/2-propanol = 99.8/0.2, 1 mL/min, 230 nm, 19.4 min (2R,3S), major, 28.4 min (2S,3R), minor.9f AUTHOR INFORMATION

Corresponding Author *E-mail: [email protected].

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ACKNOWLEDGEMENTS

M.N. thanks Mr. Kubota and Ms. Ohashi for their technical assistance. ASSOCIATED CONTENT

Supporting Information NMR spectra, HPLC charts, X-ray crystal structure details.

This material is available free of charge via the Internet

at http://pubs.acs.org. REFERENCES and FOOTNOTES

(1) Asymmetric epoxidation: Xia, Q.-H.; Ge, H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X. Chem. Rev. 2005, 105, 1603.

(2) Ti–chiral tartrate system: (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974. (b) Katsuki, T.;

Martin, V. S. Org. React. 1996, 48, 1.

(3) V–chiral HA system: (a) Michaelson, R. C.; Palermo, R. E.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 1990.

(b) Sharpless, K. B.; Verhoeven, T. R. Aldrichimca Acta 1979, 12, 63. (c) Berrisford, D. J.; Bolm, C.; Sharpless, K. B.

Angew. Chem., Int. Ed. 1995, 34, 1059.

(4) V–chiral HA system, review: (a) Bolm, C. Coordination Chem. Rev. 2003, 237, 245. (b) Licini, G.; Conte, V.;

Coletti, A.; Mba, M.; Zonta, C. Coordination Chem. Rev. 2011, 255, 2345. (c) Li, Z.; Yamamoto, H. Acc. Chem. Res.

2013, 46, 506.

(5) V–chiral HA system: (a) Murase, N.; Hoshino, Y.; Oishi, M.; Yamamoto, H. J. Org. Chem. 1999, 64, 338. (b)

Hoshino, Y.; Murase, N.; Oishi, M.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2000, 73, 1653. (c) Hoshino, Y.; Yamamoto,

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H. J. Am. Chem. Soc. 2000, 122, 10452. (d) Makita, N.; Hoshino, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 2003, 42, 941.

(6) V–chiral HA system: (a) Traber, B.; Jung, Y.-G.; Park, T. K.; Hong, J.-I. Bull. Korean Chem. Soc. 2001, 22, 547. (b) Bolm, C.; Beckmann, O.; Kühn, T.; Palazzi, C.; Adam, W.; Rao, P. B.; Saha-Möller, C. R. Tetrahedron: Asymmetry

2001, 12, 2441. (c) Bolm, C.; Kühn, T. Isr. J. Chem. 2001, 41, 263. (d) Wu, H.-L.; Uang, B.-J. Tetrahedron:

Asymmetry 2002, 13, 2625. (e) Malkov, A. V.; Bourhani, Z.; Kočovský, P. Org. Biomol. Chem. 2005, 3, 3194. (f)

Bourhani, Z.; Malkov, A. V. Chem. Commun. 2005, 4592. (g) Malkov, A. V.; Czemerys, L.; Malyshev, D. A. J. Org.

Chem. 2009, 74, 3350.

(7) V–achiral HA and chiral ROOH system: (a) Adam, W.; Beck, A. K.; Pichota, A.; Saha-Möller, C. R.; Seebach, D.; Vogl, N.; Zhang, R. Tetrahedron: Asymmetry 2003, 14, 1355. (b) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-Möller,

C. R.; Seebach, D.; Beck, A. K.; Zhang, R. J. Org. Chem. 2003, 68, 8222. (c) Lattanzi, A.; Piccirillo, S.; Scettri, A.

Eur. J. Org. Chem. 2005, 1669. (d) Lattanzi, A.; Scettri, A. J. Organomet. Chem. 2006, 691, 2072. (8) V–chiral BHA system: (a) Zhang, W.; Basak, A.; Kosugi, Y.; Hoshino, Y.; Yamamoto, H. Angew. Chem., Int. Ed.

2005, 44, 4389. (b) Zhang, W.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 286. (c) Barlan, A. U.; Zhang, W.;

Yamamoto, H. Tetrahedron 2007, 63, 6075. (d) Li, Z.; Zhang, W.; Yamamoto, H. Angew. Chem., Int. Ed. 2008, 47, 7520.

(9) Mo, Zr, Hf, W–chiral BHA system: (a) Basak, A.; Barlan, A. U.; Yamamoto, H. Tetrahedron: Asymmetry 2006, 17,

508. (b) Barlan, A. U.; Basak, A.; Yamamoto, H. Angew. Chem., Int. Ed. 2006, 45, 5849. (c) Li, Z.; Yamamoto, H. J.

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Am. Chem. Soc. 2010, 132, 7878. (d) Olivares-Romero, J. L.; Li, Z.; Yamamoto, H. J. Am. Chem. Soc. 2012, 134,

5440. (e) Olivares-Romero, J. L.; Li, Z.; Yamamoto, H. J. Am. Chem. Soc. 2013, 135, 3411. (f) Wang, C.; Yamamoto,

H. J. Am. Chem. Soc. 2014, 136, 1222.

(10) (a) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691. (b) Teichert, J. F.; Feringa, B. L. Angew. Chem. Int. Ed.

2010, 49, 2486. (c) Privileged Chiral Ligands and Catalysts; Zhou, Q.-L., Ed.; VCH: Weinheim, 2011. (11) (a) Walsh, P. J.; Kozlowski, M. C.; Fundamentals of Asymmetric Catalysis; University Science Books: Sausalito,

CA, 2008; pp 114–164. (b) Toriumi, K.; Ito, T.; Takaya, H.; Souchi, T.; Noyori, R. Acta Cryst. 1982, B38, 807. (c)

Whitesell, J. K. Chem. Rev. 1989, 89, 1581. (d) Pfaltz, A.; Drury, W. J., III Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5723.

(12) (a) Schalley, C. A.; Lützen, A.; Albrecht, M. Chem. Eur. J. 2004, 10, 1072. (b) Hatano, M.; Ishihara, K. Chem. Commun. 2012, 48, 4273. (c) Enders, D.; Nguyen, T. V. Org. Biomol. Chem. 2012, 10, 5327. (13) (a) Seki, M.; Yamada, S.; Kuroda, T.; Imashiro, R.; Shimizu, T. Synthesis 2000, 1677. (b) Ohta, T.; Ito, M.;

Inagaki, K.; Takaya, H. Tetrahedron Lett. 1993, 34, 1615. (c) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2007, 129, 10054.

(14) Please see Supporting Information.

(15) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112, 5525.

(16) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.

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(17) The enantioselectivity of the epoxidation using BBHA 2a was generally lower than those using Yamamoto's BHA ligands,8a,c but one example of epoxidation of geraniol (3f) showed a similar level of enantioselectivity.

(18) Jiang, T.; Huynh, K.; Livinghouse, T. Synlett 2013, 24, 193. (19) Hollingworth, C.; Hazari, A.; Hopkinson, M. N.; Tredwell, M.; Benedetto, E.; Huiban, M.; Gee, A. D.; Brown, J.

M.; Gouverneur, V. Angew. Chem., Int. Ed. 2011, 50, 2613.

(20) Fox, R. J.; Lalic, G.; Bergman, R. G. J. Am. Chem. Soc. 2007, 129, 14144.

(21) Knight, F. I.; Brown, J. M.; Lazzari, D.; Ricci, A.; Blacker, A. J. Tetrahedron 1997, 53, 11411.

(22) Esterification: (a) Fujihara, T.; Xu, T.; Semba, K.; Terao, J.; Tsuji, Y. Angew. Chem., Int. Ed. 2011, 50, 523.

Reduction: (b) Rahaim, R. J., Jr.; Maleczka, R. E., Jr. Org. Lett. 2011, 13, 584.

(23) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-Möller, C. R.; Seebach, D.; Zhang, R. Org. Lett. 2003, 5, 725.

(24) Denis, J.-N.; Greene, A. E.; Serra, A. A.; Luche, M.-J. J. Org. Chem. 1986, 51, 46.

(25) Wang, B.; Wong, O. A.; Zhao, M.-X.; Shi, Y. J. Org. Chem. 2008, 73, 9539.

(26) Riclea, R.; Dickschat, J. S. Chem. Eur. J. 2011, 17, 11930.

(27) Kolb, M.; Hijfte, L. V.; Ireland, R. E. Tetrahedron Lett. 1988, 29, 6769.

(28) Egami, H.; Oguma, T.; Katsuki, T. J. Am. Chem. Soc. 2010, 132, 5886.

(29) Dumont, R.; Pfander, H. Helv. Chim. Acta. 1983, 66, 814.

(30) Shafi, S. M.; Chou, J.; Kataoka, K.; Nokami, J. Org. Lett. 2005, 7, 2957.

(31) Hill, J. G.; Sharpless, K. B.; Exon, C. M.; Regenye, R. Org. Synth. 1984, 63, 66.

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(32) Nakagawa, N.; Mori, K. Agric. Biol. Chem. 1984, 48, 2505.

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Asymmetric epoxidation of allylic alcohols catalyzed by vanadium-binaphthylbishydroxamic Acid complex.

A vanadium-binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of allylic alcohols is described. The optically active binapht...
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